Ephrin type-A receptor 2/EphA2 is a member of the Eph receptor tyrosine kinase family which binds Ephrins A1, 2, 3, 4, and 5. A and B class Eph proteins have a common structural organization. Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. EphA2 becomes autophosphorylated following ligand binding and then interacts with SH2 domain-containing PI3-kinase to activate MAPK pathways. Reverse signaling is also propagated through the Ephrin ligand. Transcription of EphA2 is dependent on the expression of E-Cadherin, and can be induced by p53 family transcription factors. EphA2 is upregulated in breast, prostate, and colon cancer vascular endothelium. Its ligand, EphrinA1, is expressed by the local tumor cells. In some cases, EphA2 and EphrinA1 are expressed on the same blood vessels. EphA2 signaling cooperates with VEGF receptor signaling in promoting endothelial cell migration.